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GeneBe

10-19450384-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001142308.3(MALRD1):c.4923G>C(p.Leu1641=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00559 in 1,550,220 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0057 ( 34 hom. )

Consequence

MALRD1
NM_001142308.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.17
Variant links:
Genes affected
MALRD1 (HGNC:24331): (MAM and LDL receptor class A domain containing 1) This gene encodes a conserved protein that features multiple MAM (meprin-A5-protein tyrosine phosphatase mu) and LDLR A2 (low density lipoprotein receptor A2) domains. Expression of this gene is enriched in the small intestine and is upregulated during differentiation of a human cell line that exhibits properties of intestinal epithelial cells. The encoded protein has been shown to modulate production of FGF19 in a human intestinal cell line and may regulate bile acid metabolism in the liver. A synergistic interaction between an allele of this gene and the APOE E4 allele is associated with an elevated risk of Alzheimer's disease in human patients. [provided by RefSeq, Jul 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-19450384-G-C is Benign according to our data. Variant chr10-19450384-G-C is described in ClinVar as [Benign]. Clinvar id is 785880.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.17 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MALRD1NM_001142308.3 linkuse as main transcriptc.4923G>C p.Leu1641= synonymous_variant 29/40 ENST00000454679.7
LOC102724082XR_007062079.1 linkuse as main transcriptn.167+6191C>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MALRD1ENST00000454679.7 linkuse as main transcriptc.4923G>C p.Leu1641= synonymous_variant 29/401 NM_001142308.3 P1
MALRD1ENST00000377266.7 linkuse as main transcriptc.2953-38576G>C intron_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00497
AC:
756
AN:
152164
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000990
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00524
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.0106
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00710
Gnomad OTH
AF:
0.00863
GnomAD3 exomes
AF:
0.00458
AC:
686
AN:
149662
Hom.:
2
AF XY:
0.00460
AC XY:
370
AN XY:
80422
show subpopulations
Gnomad AFR exome
AF:
0.000875
Gnomad AMR exome
AF:
0.00199
Gnomad ASJ exome
AF:
0.00322
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00311
Gnomad FIN exome
AF:
0.00933
Gnomad NFE exome
AF:
0.00639
Gnomad OTH exome
AF:
0.00531
GnomAD4 exome
AF:
0.00565
AC:
7902
AN:
1397936
Hom.:
34
Cov.:
31
AF XY:
0.00557
AC XY:
3843
AN XY:
689468
show subpopulations
Gnomad4 AFR exome
AF:
0.000855
Gnomad4 AMR exome
AF:
0.00213
Gnomad4 ASJ exome
AF:
0.00429
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.00283
Gnomad4 FIN exome
AF:
0.00942
Gnomad4 NFE exome
AF:
0.00622
Gnomad4 OTH exome
AF:
0.00502
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00496
AC:
756
AN:
152284
Hom.:
2
Cov.:
32
AF XY:
0.00543
AC XY:
404
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.000987
Gnomad4 AMR
AF:
0.00523
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00228
Gnomad4 FIN
AF:
0.0106
Gnomad4 NFE
AF:
0.00710
Gnomad4 OTH
AF:
0.00854
Alfa
AF:
0.00488
Hom.:
1
Bravo
AF:
0.00418
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 17, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
Cadd
Benign
0.26
Dann
Benign
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs117117480; hg19: chr10-19739313; API